Identification of benzazole compounds that induce HIV-1 transcription

Graci, Jason D.; Michaels, Daniel; Chen, Guangming; Lester, Gillian M. Schiralli; Nodder, Sarah B.; Weetall, Marla; Karp, Gary M.; Gu, Zhengxian; Colacino, Joseph M.; Henderson, Andrew J.

doi:10.1371/journal.pone.0179100

Cited by 3 publications

(3 citation statements)

References 82 publications

(79 reference statements)

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“…They were not HDACIs and the HIV-1 transcription was driven neither by the NF-κB signaling pathway nor by stimulating of HIV-1 LTR. These data indicated that benzazole might be a promising chemotype to be developed into potent LRAs with appropriate chemical optimizations and further investigation into the mechanism of actions [128].…”

Section: Benzazole Derivativementioning

confidence: 97%

Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation

Wang

Wei

et al. 2022

Molecules

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The existence of latent viral reservoirs (LVRs), also called latent cells, has long been an acknowledged stubborn hurdle for effective treatment of HIV-1/AIDS. This stable and heterogeneous reservoir, which mainly exists in resting memory CD4+ T cells, is not only resistant to highly active antiretroviral therapy (HAART) but cannot be detected by the immune system, leading to rapid drug resistance and viral rebound once antiviral treatment is interrupted. Accordingly, various functional cure strategies have been proposed to combat this barrier, among which one of the widely accepted and utilized protocols is the so-called ‘shock-and-kill’ regimen. The protocol begins with latency-reversing agents (LRAs), either alone or in combination, to reactivate the latent HIV-1 proviruses, then eliminates them by viral cytopathic mechanisms (e.g., currently available antiviral drugs) or by the immune killing function of the immune system (e.g., NK and CD8+ T cells). In this review, we focuse on the currently explored small molecular LRAs, with emphasis on their mechanism-directed drug targets, binding modes and structure-relationship activity (SAR) profiles, aiming to provide safer and more effective remedies for treating HIV-1 infection.

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Section: Benzazole Derivativementioning

confidence: 97%

Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation

Wang

Wei

et al. 2022

Molecules

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“…Cytokines/receptor agonists IL IL-2, IL-7, IL-15 [31] TCR/Co-receptor activators Maraviroc [32] TLR agonists TLR2, 3, 7, 8, 9 agonists [33] Epigenetic modifiers HDAC inhibitors Vorinistat, panobinostat, AR-42, MS-275, chidamide HDAC1, 2, 3 [34][35][36][37][38] Histone methyltransferase inhibitors Chaetocin, AZ505 Suv39H1, SMYD2 [39,40] Intracellular signaling modulators PKC agonists Ingenol EK-16A, gnidimacrin, bryostatin, SUW133, PEP005/Inge-nol-3angelate, Prostratin, Bryostatin-1, IDB NF-kappaB [41][42][43] AMPK activators Dibutyryl-cAMP [44] JAK/STAT agonists Benzotriazole, benzazole STAT3 [45,46] IAP agonists Debio1143 NF-kappaB (non-canonical) [47] Transcriptional elongation regulators BET inhibitors JQ1, MMQO, UMB-136, RVX-208, PFI-1, OTX015…”

Section: Referencesmentioning

confidence: 99%

Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure

Zaongo¹,

Ma²,

Song³

et al. 2021

Chinese Medical Journal

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Many seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as “selective elimination of host cells capable of producing HIV” (SECH). Similar to the “shock and kill strategy,” the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.

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“…Therefore, these compounds have been widely studied in diverse areas of chemistry. Some of important pharmacological activities of these heterocycles include of being anticancer, [ 1 ] antitumor, [ 2 ] anticonvulsant, [ 3 ] anti‐Parkinson, [ 4 ] anti‐Alzheimer, [ 5 ] anti‐HIV, [ 6 ] anti‐helminthic, [ 7 ] antifungal, [ 8 ] antibacterial, [ 9 ] antimicrobial, [ 10 ] antiviral, [ 11 ] and antihistaminic. [ 12 ] Because of such attractive applications, many studies have focused on the development of new synthetic benzazoles methodologies.…”

Section: Introductionmentioning

confidence: 99%

New phosphonium bromobismuthate as selective catalytic reagent in the heterocyclization reactions

Salmasi

Gholizadeh

Salimi

et al. 2023

Applied Organom Chemis

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A new hybrid phosphonium bromobismuthate compound was synthesized and characterized by 1H NMR, 13C NMR, 31P NMR, FT‐IR, differential scanning calorimetry (DSC) and single‐crystal X‐ray diffraction analysis. The crystal packing structures of title compound were stabilized by various intermolecular interactions especially of the type CH···Br hydrogen bonds between phosphonium cations and [Bi2Br9]3− anion. The relative contribution of various close contacts and 2D fingerprint plots of title compound and three analogous structures obtained from Cambridge Structural Database (CSD) were investigated by Hirshfeld surface analysis. Furthermore, the catalytic activity of title compound was investigated in heterocyclization reaction for the synthesis of significant and pharmacologically useful benzimidazole and benzoxazole derivatives. The results indicated that the yields of the product for aldehydes bearing p‐substituents and o‐substituents were higher than for m‐substituent ones. In addition to selectivity, simplicity of operation, waste minimization, ease of manipulation, short reaction time, excellent yield of product, and easy workup, this technique uses title compound as the catalyst, which is green, recyclable, soft, remarkably nontoxic, and easy to handle.

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Identification of benzazole compounds that induce HIV-1 transcription

Cited by 3 publications

References 82 publications

Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation

Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation

Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure

New phosphonium bromobismuthate as selective catalytic reagent in the heterocyclization reactions

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